Infection of Escherichia coli by R23 results in a coordinate repression of permease and β-galactosidase genes of the lactose operon but this effect is not mediated at the level of the regulatory or promoter genes. Immediately preceding the inhibitory phase there is a transient phase of increased inducer uptake and enzyme synthesis which may be attributed to permeability changes resulting from R23 infection. After this period there is an initial, relatively small decrease in β-galactosidase synthesis which is dependent on phage adsorption but not on viral RNA penetration. A more severe repression of β-galactosidase synthesis begins about 25 min after infection and becomes more pronounced over the next 30 min; this phase of inhibition is dependent on viral RNA penetration and expression of at least the RNA synthetase cistron.